P1216: ZANUBRUTINIB PLUS R-CHOP(RI-CHOP) AS THE TREATMENT FOR DOUBLE EXPRESSION OF MYC/BCL2 IN PATIENTS WITH DIFFUSED LARGE B-CELL LYMPHOMA
Authors: K. Ren, L. zou, M. jiang, W. wu, X. chen, T. hai, Q. luo
Journal: HemaSphere (2022)

Background: Diffuse large B cell lymphoma (DLBCL) with double expression of MYC and BCL2 proteins (DE-DLBCL) is an aggressive disease. The incidence of double expressor status in DLBCL was 20～30%.BCL2 overexpression was more frequent in Chinese compared with Western cases in the non-GCB subgroup. MYC/BCL2 co-expression is an adverse predictive factor for response to chemotherapy regimens, and associateswith a significantly lower probability of complete remission. Aims: To investigate a prognostic significance of MYC/BCL2 double expression in DLBCL patients treated with intensive chemotherapy RI-CHOP, we conducted this single-arm prospective study. Methods: We enrolled 31 patients aged 18 to 70 years old with double expressor status in DLBCL (DE-DLBCL) underwent modified protocol of intensive chemotherapy – zanubrutinib plus R-CHOP(RI-CHOP) in West China Hospital between 2020 and 2021 years were included in the study. We used the cutoff values of protein co-expression are 50% for BCL2 and 40% for MYC. This study excluded DE-DLBCL With c-MYC 、BCL2 or BCL6 rearrangements and Central nervous system involvement. Oral zanubrutinib was given continuously (160mg twice daily) from Day 1. Patients were administered intravenously rituximab, cyclophosphamide doxorubicin, vincristine,and prednisone. All patients were recommended to receive 6 cycles of RI-CHOP. Patients received oral ciprofloxacin (500 mg daily on Day 3-13) to prevent bacterial infection.CT/PET-CT scans were conducted to assess efficacy in 2,4,6 cycles. Four cycles of intrathecal methotrexate administration (15 mg) were performed for patients with a high CNS-IPI score and/or lymphoma-risk factors warranting CNS prophylaxis.The primary endpoint was overall response rate (ORR), after mid-term and 6 cycles. The secondary endpoint was complete response ratio (CR) and adverse events (AE). AEs were graded according to CTCAE (version 5.0). Results: 31 treatment-naïve DE-DLBCL patients diagnosed in West China hospital were enrolled in this cohort between April 2020 and December 2021. The median age of patients was 56 years old, all patients had ECOG performance ≤2.Germinal center B cell-like DLBCL (GCB) and non-GCB subtypes were found in (5/31) and (26/31), respectively. Extranodal involvement was found in 17 patients (54.8%), which the sites of extranodal involvement were the gastrointestine (3/31), bone marrow (5/31), nasal cavity (5/31),breast(2/31),testicle (1/31), renal(1/31),Vertebral body(1/31),Uterine appendage(1/31). 7 patients were classified as high-intermediate and high-risk group according to CNS-IPI. At data cutoff (December, 2021), the median follow-up was 10.5 months (2.2-19.1months) with all patients have completed at least 2 cycles. Patients received a median of 5 cycles (range 2–6 cycles),and midterm assessment could be conducted.The ORR was 100.0%, with 19 patients achieved CR (19/31),14 patients achieved PR (12/31). 2 patients developed tumor recurrence after achieved CR within one year.The most common 3-4 level AEs with RI-CHOP were neutrophil count decreased(14/31), thrombocytopenia(5/31) and typically occurred within the 4~6 cycles. Other 1-2 level toxicity events were subcutaneous hemorrhage(4/31),nausea(18/31),fatigue(10/31)and reactivation of varicella zoster virus(3/31). Two patients discontinued oral Zanubrutinib due to oral ulceration and hematuria. Image:Summary/Conclusion: RI-CHOP could be one of the promising choice for DE-DLBCL patients with fair physical condition,and could achieve high ORR and CRR. This study demonstrated a manageable safety profile of the combination regimen.